Binding of TRH, DN -1417 and MK-771 to TRH Receptors in the Rat Brain:Relationship to their central actions
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概要
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There are at least two types of [<SUP>3</SUP>H]TRH binding sites in the rat brain. High-affinity sites are regulated by GTP in an inhibitory manner. TRH, MK-771 and DN-1417 have high affinities for the high-affinity sites. MK-771 and DN-1417 have, however, much less affinity than TRH at the low-affinity binding sites. As MK-771 and DN-1417 are more potent in central activities and equipotent (MK-771) or less potent (DN-1417) in neuroendocrine activities, it was suggested that the high-affinity [<SUP>3</SUP>H]TRH binding sites are the putative TRH receptors which mediate the central actions. The low-affinity [<SUP>3</SUP>H]TRH binding sites have characteristics similar to the pituitary TRH receptors. High-affinity sites were not seen in [<SUP>3</SUP>H]-(methyl-histidyl)-TRH ([<SUP>3</SUP>H] MeTRH) binding experiments. MeTRH has potent neuroendocrine activity, unlike MK-771 and DN-1417. It is possible that [<SUP>3</SUP>H]MeTRH labels only the pituitary-type TRH receptors, but not the receptors which are involeved in the central actions of TRH.Durch die Bindungsstudien zeigten sich zwei Typen der [<SUP>3</SUP>H]TRH-Bindungsstellen im Rattengehirn. Der eine zeigte eine höhere Affinität als der andere, und wurde durch GTP hemmend reguliert. TRH, MK-771 and DN-1417, die künstliche Analoga des TRH, hatten eine gleich hohe Affinität an den hoch-affinen Bindungsstellen, jedoch waren MK-771 und DN-1417 viel weniger-affinitiv als TRH an den schwach-affinen Bindungsstellen. Da MK-771 und DN-1417 stärkere Zentralwirkungen und schwächere Neuro-endokrinwirkungen als TRH besitzen, wurde angenommen, dass die hoch-affinen [<SUP>3</SUP>H]TRH-Bindungsstellen die putativen TRH-Rezeptoren sind, die ihre Zentralwirkungen vermitteln, and dass die schwach-affinen [<SUP>3</SUP>H]TRH-Bindungsstellen eine Bindeeigenschaft besitzten, die den hypophysischen TRH-Rezeptoren ähnlich ist. Die hoch-affinen Bindungsstellen waren nicht im [<SUP>3</SUP>H]-(methyl-histidyl) -TRH ([<SUP>3</SUP>H]MeTRH) Bindungsexperiment nachweisbar. Dass das MeTRH eine starke Neuroendokrin-Aktivität hat, ist eine gegenteilige Wirkeigenschaft des MK-771 und des DN-1417. Es kann deswegen vernünftig sein anzunehmen, dass [<SUP>3</SUP>H]MeTRH nur die Hypophyse-ähnlichen TRH-Rezeptoren im Gehirn labelliert, aber nicht die Rezeptoren labelliert, die die Zentralwirkungen vermitteln.
- 久留米大学医学部 The Kurume Medical Journal 編集部の論文
著者
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INANAGA Kazutoyo
Department of Nernropsychiatry and Institute of Brain Diseases, Kurume University School of Medicine
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FUNATSU KUNIHIKO
Department of Neuropsychiatry, Kurume University School of Medicine
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TESHIMA SHIGEKI
Department of Neuropsychiatry, Kurume University School of Medicine
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